Predicting Prostate Biopsy Results Using a Panel of Plasma and Urine Biomarkers Combined in a Scoring System

Abstract

Background: Determining the need for prostate biopsy is frequently difficult and more objective criteria are needed to predict the presence of high grade prostate cancer (PCa). To reduce the rate of unnecessary biopsies, we explored the potential of using biomarkers in urine and plasma to develop a scoring system to predict prostate biopsy results and the presence of high grade PCa.Methods: Urine and plasma specimens were collected from 319 patients recommended for prostate biopsies. We measured the gene expression levels of UAP1, PDLIM5, IMPDH2, HSPD1, PCA3, PSA, TMPRSS2, ERG, GAPDH, B2M, AR, and PTEN in plasma and urine. Patient age, serum prostate-specific antigen (sPSA) level, and biomarkers data were used to develop two independent algorithms, one for predicting the presence of PCa and the other for predicting high-grade PCa (Gleason score [GS] ≥7).Results: Using training and validation data sets, a model for predicting the outcome of PCa biopsy was developed with an area under receiver operating characteristic curve (AUROC) of 0.87. The positive and negative predictive values (PPV and NPV) were 87% and 63%, respectively. We then developed a second algorithm to identify patients with high-grade PCa (GS ≥7). This algorithm's AUROC was 0.80, and had a PPV and NPV of 56% and 77%, respectively. Patients who demonstrated concordant results using both algorithms showed a sensitivity of 84% and specificity of 93% for predicting high-grade aggressive PCa. Thus, the use of both algorithms resulted in a PPV of 90% and NPV of 89% for predicting high-grade PCa with toleration of some low-grade PCa (GS <7) being detected.Conclusions: This model of a biomarker panel with algorithmic interpretation can be used as a “liquid biopsy” to reduce the need for unnecessary tissue biopsies, and help to guide appropriate treatment decisions.

Improving the evaluation and diagnosis of clinically significant prostate cancer in 2017

“…A recent 2016 study on 319 patients with indication for prostate biopsy measured a panel of gene expression levels (“liquid biopsy”) in plasma and urine (UAP1, PDLIM5, IMPDH2, HSPD1, PCA3, PSA, TMPRSS2, ERG, GAPDH, B2M, AR, and PTEN), along with serum PSA and age, to screen for best biomarker combinations to predict high-grade PC in a multivariable logistic model[48]. The AUC for the 13 variables was 0.85, and 0.80 if only eight were included.…”

Comparative analysis of the PCA3 gene expression in sediments and exosomes isolated from urine

“…Одна из них включала гены РСА3, ELF3, SPP1 и HIST1H2BG, другая -PCA3 и TMPRSS2: ERG с ис-пользованием Progensa и новой тест-системы Т2ERG (Hologic), еще в одной работе анализировали экспрес-сию 12 генов [26][27][28]. Опубликованы панели экспрес-сионных маркеров без РСА3, также направленные на диагностику РПЖ по осадку мочи, которые вклю-чают гены DLX1 и HOXC6 [29][30][31].…”

Prostatectomy‐based validation of combined urine and plasma test for predicting high grade prostate cancer

“…We recently reported the development of a combined urine/plasma assay that has been shown to predict PCa GS ≥ 3 + 4 as compared with Bx‐derived GS. This test measures the expression levels of 10 different genes in urine and plasma and incorporates these measurements in an algorithm that includes serum PSA (sPSA), prostate size, history of prior biopsy, ethnic background, and age . The PCa specific‐genes included in this test are UAP1 , PDLIM5 , IMPDH2 , HSPD1 , PSA , PCA3 , TMPRSS2 , ERG , AR , and PTEN , which have been previously associated with progression, recurrence, and metastasis in PCa .…”

“…Analysis of the housekeeping genes GAPDH and B2M in urine and plasma is also performed and used for normalization. We combined urine/plasma biomarkers with clinical information in logistic model and developed a scoring system to predict prostate biopsy results and the presence of high grade PCa . In the current prospective study, we examined the reliability of this urine/plasma test in predicting the presence of high grade PCa as confirmed by prostatectomy.…”